Project Summary: The aim of our interdisciplinary Institutional Training Program in Neurodevelopmental Disabilities, based at The Children's Hospital of Philadelphia (CHOP) and The University of Pennsylvania (U of P), is to train MD and PhD pre-/post-doctoral fellows in research focused on genetic and acquired disorders that cause mental retardation and developmental disability. Twenty-seven mentors will participate in this second competitive renewal of this program;20 are based primarily at CHOP, and 7 primarily at the U of P. All are heavily involved in biomedical graduate education and are closely interlinked by mutual research projects and grants. In addition to mentored research training, our curriculum emphasizes: 1) a clinical practicum requirement for both MDs and PhDs, 2) formal course work through the U of P Graduate Studies Program, 3) training in responsible conduct of research, 4) training in biostatistics and 5) workshops that cover a variety of important survival skills, including scientific writing, public presentations, grant writing workshops, laboratory management, and career advancement skills. During the first 9 years of our program, we accepted 19 Trainees;4 were MDs, 14 were PhDs, and 1 was a MD/PhD. 11 of these trainees were female and 4 of these trainees were under-represented minorities. Of the 14 who have completed training, 8 are in faculty positions, 2 are continuing their training at other academic institutions, 1 is a senior research scientist at a pharmaceutical company, 1 is a scientific administrator, and 1 is in private practice. We request continued support for 4 postdoctoral fellows/year and would like to expand our program to include support for 2 pre-doctoral fellows/year. Our goal remains focused on providing a training program unlike any other here at the CHOP or the U of P that is focused on acquired and genetic causes of developmental disability. This program benefits from being in an outstanding environment that commits substantial resources to training, to basic biomedical research, and to a true 'bench to bedside'approach to translational research. Project Relevance: It has been estimated that developmental disabilities affect 10% of all families in the USA. Researchers are urgently needed who are willing and able to apply modern research methods to elucidating the pathogenesis and pathophysiology of these disorders, so that new and more effective therapeutic interventions can be identified. This program strives to fill this need.